Journal
INFLAMMATION RESEARCH
Volume 57, Issue 7, Pages 329-339Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00011-007-7220-1
Keywords
JNK; p38 MAPK; IL-8; p53; NF-kappa B p65
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Objective: It is reported that Nuclear factor-kappa B (NF-kappa B) activation is dysregulated in chronic inflammatory diseases like psoriasis, rheumatoid arthritis and cancer, resulting in an over expression of pro-inflammatory cytokines and an inhibition of apoptosis. We studied NF-kappa B activation and the induction of interleukin 8 (IL-8) and p53 gene expression in an interleukin 1 beta (IL-1 beta) stimulated HepG2 cell line. Methods: NF-kappa B induced IL-8 and p53 protein production was studied using specific siRNA, an I kappa B kinase 2 inhibitor, and mitogen activated protein kinase (MAPK) inhibitors. Results were analyzed by different techniques including Western blotting and ELISA. Results: IL-1 beta induced both the IL-8 and p53 mRNA expression and protein production of IL-8, but not p53. Knockdown of NF-kappa B p65 expression with siRNA strongly reduced IL-8 production and significantly induced protein levels of p53. An I kappa B kinase 2 inhibitor, sc514, also strongly reduced IL-8 and significantly induced p53 protein levels. Using three MAPK inhibitors we showed that p38 MAPK and JNK dependent mechanisms are involved in the regulation of the IL-8 and p53 protein expression. Conclusion: Our results indicate that IL-8 and p53 protein expression is regulated through inverse activation of the p38 MAPK and the JNK pathways and the NF-kappa B p65 expression.
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